Thyroid hormone (Triiodothyronine; T3) is an important endocrine signaling hormone and it is essential for normal development, differentiation and maintenance of metabolic balance in mammals. Natural thyroid hormone, T3 exhibit its physiological effect by acting on a Thyroid Hormone Receptor (THR), which belongs to the nuclear hormone receptor super family. There are two different isoforms of Thyroid Hormone Receptors, THR-α and THR-β. Further these two isoforms are sub-classified as α1; α2 and β1; β2 subtypes. THRβ1 is prevalent in liver (85%), while THR α1 is mainly present in cardiac tissue (Yen P. M., Physiol. Rev; 81 (2001) 1097-1142).
At normal levels, T3 maintains bodyweight, metabolic rate, body temperature, mood and regulate serum cholesterol. Hypothyroidism is associated with weight gain, high levels of low-density lipoproteins (LDL) cholesterol and depression. Hyperthyroidism leads to weight loss, hypermetabolism, lowering of serum LDL levels, cardiac arrhythmia, heart failure, muscle weakness, bone loss and anxiety.
The natural thyroid hormone T3 does not show any selectivity in binding to both of the THR isoforms (THRα1 and THR β1). Thus, administration of T3 lowers plasma cholesterol, low-density lipoprotein (LDL) and triglyceride levels in animal models and humans. However, T3 cannot be used therapeutically to treat hypercholesterolemia and obesity due to its cardiac side effects. However, knockout animal studies as well as results with some selective ligands suggest that such cardiac side effects can be attributed to the THR α1 isoform. Thus some effects of T3 may be therapeutically useful in non-thyroid disorders if adverse effects can be minimized or eliminated. These potentially useful influences include weight reduction, lowering of serum LDL levels, amelioration of depression and stimulation of bone formation (Cheng S., Steroids; 70 (2005); 450-454).
Development of specific and selective thyroid hormone receptor ligands, particularly THR β1 agonist could lead to specific therapies for disorders such as obesity and hyperlipidemia, while avoiding the cardiovascular and other toxicities of native thyroid hormones. Thus, compounds mimicking only the beneficial effects of the thyroid hormone and lacking their cardiac side effects (tachycardia and arrhythmia) potentially could be used to treat a number of conditions such as obesity and dyslipidemia. In this regard, THR agonists that interact selectively with the β1 isoform of the THR offer an especially attractive method for avoiding cardio-toxicity (J. D. Baxter; Trends Endocrinol. Metab., 15 (2004); 154-157).
Various compounds have been disclosed as possible agonists of THR β. Some of the more relevant ones for the present invention includes WO2007039125, WO 0039077, US20040157844 which are incorporated herein as reference.
US20020035153 describes compounds of the following general formula as Thyromimetics.

However, none of these compounds have been commercially developed and looking at the beneficial potential and medical need for such compounds, there remains a need for developing further compounds with better therapeutic and/or safety profile. Herein, we disclose novel compounds which shows activity as THR β agonists.